Objective.—Suicide by drug overdose is a major public health problem, and antidepressant medications are the most common agent involved. European studies suggest differences in the rates of suicide by overdose among antidepressants, but no reports have been published for the United States. We estimated the comparative risks of suicide attempts and suicides, and the relative risk of fatality in the event of an overdose for the major antidepressants currently marketed in the United States.

Data Sources.—Information regarding suicide attempts and suicides by antidepressant overdose was obtained from the published reports of the Drug Abuse and Warning Network and the annual report of the American Association of Poison Control Centers, and corrected for differences in total annual prescriptions using data from the National Prescription Audit.

Results.—The risk of a suicide attempt did not appear to differ among antidepressants. The tricyclic antidepressants were associated with a higher rate of death in the event of an overdose than the newer nontricyclic antidepressants in both the annual report of the American Association of Poison Control Centers and the Drug Abuse and Warning Network data. The chance of death after an overdose was greater for desipramine hydrochloride than for other tricyclics.

Conclusion.—The higher risk of suicide with tricyclics vs nontricyclics may be explained by a higher rate of death from overdose rather than more suicide attempts. Tricyclics carry the risk of greater cardiotoxicity. The basis for the even higher rate of death/overdose of desipramine is not known and requires further research. If these findings are replicated in a case-control study design, they have important implications for the choice of an antidepressant for the depressed patient at risk for suicidal behavior.(JAMA. 1992;268:3441-3445)